1,721,001 research outputs found
BASIC AND TRANSLATIONAL ASPECTS OF CELL-BASED APPROACHES FOR EARLY AND LATE STAGE OSTEOARTHRITIS
Full text linkOsteoarthritis (OA) is a highly disabling pathology which is worldwide investigated by the scientific community due to its increasing diffusion. The incidence of this age-related disease is increasing with population ageing and worldwide estimates indicate that 9.6% of men and 18% of women with more than 60 years present OA-related symptoms.
Osteoarthritis induces the progressive damage of articular cartilage and subchondral bone and can eventually lead to the complete loss of joint functionality. Nowadays, the management of OA includes non-pharmacological, pharmacological, and surgical treatments. Non pharmacological approaches include exercise, weight loss, and physiotherapy and are used in conjunction with pharmacological treatments. The pharmacological management of OA patients is mainly based on the use of anti-inflammatory drugs for pain control. Hence, the pharmacological approach to OA patients is synptomatic, but not resolutive, since it is not able to alter the progression of the disease. These therapeutical options are not suitable for late stage OA patients, whereby the severe pain and the functional limitations caused by advanced OA degeneration are currently resolved by joint replacement.
Due to the low self-repair ability of articular cartilage, untreated cartilage lesions can easily degenerate into OA. Different strategies have been developed to treat promptly chondral lesions, comprising cell-based therapies, such as autologous chondrocyte implantation (ACI). These cell-based therapies have been recently proposed also for the treatment of early OA patients in order to overcome or at least delay the need for a more invasive intervention such as joint replacement.
However, major issues associated to the clinical use of autologous articular chondrocytes (ACs) are the limited number of cell harvestable from a small cartilage biopsy and the de-differentiation process occurring during the expansion phase required to achieve a clinically relevant number of cells. Furthermore, advanced age and pathological state of joints negatively affect the chondrogenic potential of ACs, representing important factors to be considered when applying chondrocyte-based therapies in particular categories of patients. In view of a possible use of autologous cell-based therapies for OA patients, we analyzed specific features of ACs as cellular yield, cell doubling rates and the dependence between these parameters and patient-related data in a set of 211 OA patients undergoing total joint replacement (Chapter 3). The patient age was not statistically correlated to the cellular yield, but was negatively correlated with the proliferation rate. No significant correlation was observed between the level of cartilage degeneration (ICRS score) and cellular yield and proliferation rates. However, in samples with the highest degree of cartilage degeneration (ICRS score 4) the cellular yield was lower compared to the other three groups (ICRS scores 1-3). In conclusion, we found that age and degenerative state of cartilage affect some basic parameter of articular chondrocytes and should be considered when evaluating the quality of the cell source to be used in clinical applications.
To overcome some of the limitations related to the use of ACs, mesenchymal stem cells (MSCs) present in several tissues, such as bone marrow and fat, have been proposed as cell candidate for cartilage treatment thanks to their demonstrated chondrogenic ability. When developing treatments for knee chondral lesions, infrapatellar fat pad and knee subcutaneous adipose tissue, two fat depots easily accessible during knee surgery, can be considered appealing sources for MSCs harvesting. We performed a donor-matched comparison between infrapatellar fat pad MSCs (IFP-MSCs) and knee subcutaneous adipose tissue stem cells (ASCs) obtained from OA patients undergoing total knee replacement, analyzing their immunophenotype and multi-differentiative ability, with a focus on their osteogenic and chondrogenic potential (Chapter 4). We found that these cell populations share common features at the undifferentiated state, such as immunophenotype and clonogenic potential, but display a specific commitment towards the osteogenic and chondrogenic lineage. Indeed, significantly higher levels of osteogenic markers, as calcified matrix deposition and alkaline phosphatase activity, were found in ASCs, highlighting the superior osteogenic commitment of this cell population in comparison with IFP-MSCs. Conversely, IFP-MSCs differentiated towards the chondrogenic lineage by 3D pellet culture showed greater glycosaminoglycans (GAGs) deposition and higher expression of chondrogenic genes as aggrecan (ACAN) and type II collagen (COL2A1) compared to ASCs pellets, revealing a superior chondrogenic potential. This result was supported by lower expression of hyperthrophic and fibrotic markers, as type X (COL10A1) and type I (COL1A1) collagen, in IFP-MSCs pellets compared to ASCs. The observed dissimilarities indicate that populations of adipose-derived MSCs harvested from different anatomical sites have specific features that suggest their preferential use for specific cell-based applications.
In the last decade, the co-culture of ACs and MSCs has gained growing interest to investigate the cross-talk between these cell types and to evaluate the possibility of replacing a fraction of ACs with MSCs, in order to reduce the in vitro expansion phase of ACs and subsequently limit their de-differentiation. Controversial results have been reported on the possibility to generate cartilage-like matrix by co-culturing ACs and MSCs, indicating a prominent role for the origin and de-differentiation state of chondrocytes as determinants of the outcomes. We evaluated whether the co-culture of IFP-MSCs and ASCs with a small fraction of ACs was able to lead to cartilage-like matrix generation and to the expression of chondrogenic markers comparable to ACs (Chapter 5). To better resemble a possible clinical application of this strategy we performed autologous co-cultures combining IFP-MSCs and ASCs with expanded and cryo-preserved donor-matched ACs and we used cells derived from OA patients so as not to neglect the impact of the pathological and de-differentiated state of ACs on the outcome of the co-cultures. Chondrogenic genes SRY (sex determining region Y)-box 9 (SOX9), COL2A1, and ACAN were less expressed in co-cultures compared to ACs mono-cultures. No significant differences were observed for GAGs/DNA in mono-cultures, demonstrating the reduced chondrogenic potential of ACs, probably deriving by both their pathological origin and their de-differentiated state. Total GAGs content in co-cultures did not differ significantly from values predicted as the sum of each cell type contribution corrected for the co-culture ratio, as confirmed by histology. Therefore, a small percentage of expanded and cryopreserved ACs did not lead to IFP-MSCs and ASCs chondro-induction. Our results suggest that chondrogenic potential and origin of chondrocytes play a relevant role in the outcome of co-cultures, indicating the need for further investigations to demonstrate their clinical relevance in the treatment of aged osteoarthritic patients.
As aforementioned, chondrogenic differentiation of both ACs and MSCs is usually performed in 3D culture models that partially mimic the 3D environment of cartilagineous matrix such as culture in pellets and in 3D scaffolds. Pellet culture is widely used in the field of cartilage tissue engineering to test and optimize differentiation protocols. These experiments normally require to prepare replicates from a relevant number of donors to investigate different culture conditions. Unfortunately, handling a high number of samples in 3D pellet culture is extremely time consuming and is a major issue in experiments with many different conditions. To overcome these limitations, we exploited low-cost rapid prototyping techniques, such as laser ablation and replica molding, to generate multi-well chips in polydimethylsiloxane (PDMS) for the formation and culture of cell aggregates (Chapter 6). Each PDMS chip allowed the simultaneous culture of several pellets leading to a significant reduction in the time required for pellet seeding and medium refresh operations. Proliferation and metabolic activity were comparable between pellets of ACs cultured in PDMS chips and pellets cultured in polypropylene tubes, whereas type II collagen deposition was increased in pellets cultured in the PDMS chips. The same rapid prototyping approach was applied to generate a patterned scaffold. As a proof of concept, we biofabricated a multi-well implantable constructs using clinically approved fibrin glue. We demonstrated that regions with different cell densities can be generated within the construct and that cells can be distributed in a spatially controlled way. These multi-well implantable scaffolds can be seeded with multiple cell types allowing the precise distribution of different cell populations, thus representing a useful tool to investigate in vitro and in vivo cell interactions in a 3D environment.
The introduction of engineered tissue into the clinical practice implies the achievement of high quality and safety standards. The use of automated bioreactor-based manufacturing can significantly increase the reproducibility of the results, being minimally affected by operator variability. Furthermore dynamic culture systems, such as perfusion bioreactors, represent a smart approach to overcome the limitations encountered in the static culture of 3D constructs having clinically relevant dimensions. Indeed, perfusion bioreactors have been shown to increase the homogeneity of cell distribution within the scaffold compared to static cell seeding. Perfusion culture provides a continuous and homogeneous influx of fresh medium throughout the construct, improving the quality and homogeneity of the extracellular matrix. The use of optimized protocols for the expansion and re-differentiation of ACs employing clinically approved growth factors is another key step to achieve a successful outcome and to grant the clinical translability of the results. Thus, in collaboration with the group supervised by Prof. Frédéric Mallein-Gerin (Institut de Biologie et Chimie des Proteines, Lyon, France) we tested the combination of a specific cocktail of clinically approved growth factors with a bi-directional perfusion bioreactor (OPB, Oscillating Perfusion Bioreactor) with the aim of improving cartilage matrix production (Chapter 7). We established a perfusion program including phases of high and low perfusion speeds to alternate sequences of cell stimulation and matrix deposition and we compared collagen sponges seeded and cultured in dynamic conditions with sponges seeded and cultured in standard static conditions. We found that perfusion improved cartilage matrix deposition within the sponges, in comparison with static conditions. More precisely, in the sponges cultured in the bioreactor a cartilaginous matrix rich in type II and type IX collagen and GAGs, with no signs of hypertrophy, was produced. Furthermore, a lower amount of type I collagen was produced in the sponges cultured in dynamic conditions, indicating that perfusion limits the risk of fibrocartilage formation. In conclusions, the dynamic culture by means of a perfusion bioreactor combined with the use of a cocktail of clinically approved growth factors proved to be effective for the generation of engineered cartilagineous grafts, improving the homogeneity and quality of the extracellular matrix generated by articular chondrocytes seeded within collagen sponges.
Aged patients with late stage OA involving an extensive erosion of articular cartilage and exposure of the underlying subchondral bone cannot be treated with cell-based therapies or standard surgical approaches aiming at cartilage restoration. In these patients, joint replacement is currently the only clinical option to restore the articular function. The insufficient implant stability is an important determinant in the failure of cementless prostheses, leading to an increase in the risk of implant mobilization and in the number of revision procedures, with major drawbacks for patients and for National Health Systems. With the aim of increasing implant osseointegration, porous metallic materials have been developed and applied to cementless implant technology to maximize bone ingrowth and bone-implant contact. More recently, the enrichment of porous titanium with growth factors has been proposed as a novel strategy to further improve implant osseointegration. We combined a macroporous titanium (Trabecular TitaniumTM, TT), currently used in the clinical practice, with a biocompatible hydrogel (amidated carboxymethylcellulose, CMCA) able to encapsulate osteoinductive factors and osteoprogenitor cells (Chapter 8). In particular, we chose strontium as osteoinductive factor and bone-marrow derived MSCs (BMSCs) as osteogenic progenitor cells for implant enrichment. We tested different concentrations of SrCl2 to select the optimal concentration to induce BMSCs differentiation. We found that SrCl2 at 5 μg/ml significantly increased calcified matrix deposition, type I collagen (COL1A1) expression and alkaline phosphatase activity, being the most effective concentration among the ones tested. The enrichment of TT with CMCA (TT+CMCA) significantly increased cell retention within the implant, representing an important improvement in view of a future clinical application of the bioactive implant. Furthermore, we found that BMSCs cultured in TT+CMCA in the presence of SrCl2 underwent a more efficient osteogenic differentiation, as demonstrated by higher alkaline phosphatase activity and calcium levels. Based on these in vitro results, we performed an in vivo study to evaluate the performance of the bioactive implant generated combining the macroporous titanium with strontium-enriched CMCA and BMSCs (Chapter 9). To mimic implant-bone interaction, an ectopic model was developed grafting TT implants into decellularized bone seeded with human BMSCs. TT was loaded or not with strontium-enriched CMCA and/or BMSCs and constructs were implanted subcutaneously in athymic mice. Osteodeposition at the bone-implant interface was investigated with fluorescence imaging, micro-CT, scanning electron microscopy (SEM), histology and biomechanical testing at different time points. Micro-CT analysis demonstrated the homogeneity of the engineered bone in all groups, supporting the reproducibility of the ectopic model. Fluorescence imaging, histology, SEM and pull-out mechanical testing showed superior tissue ingrowth in TT implants loaded with both strontium-enriched CMCA and BMSCs. In our model, the synergic action of the bioactive hydrogel and BMSCs increased both bone deposition and TT integration, indicating that the generation of bioactive implants able to promote bone deposition is a promising strategy for the improvement of implant osseointegration.
Joint inflammation is an important trait of osteoarthritis, indeed synovitis is observed in various degrees in OA patients, with OA synovium showing a mixed inflammatory infiltrate mainly consisting of macrophages. The central role of macrophages in OA evolution supports the interest in investigating their response to signals typical of OA joints, such as the ones contained in the synovial fluid (SF) of OA patients. In collaboration with the Connective Tissue Cells and Repair group supervised by Prof. Gerjo J.V.M. van Osch (Erasmus MC, Rotterdam, The Netherlands), we investigated the effect of SF from OA patients on the transcriptional expression of anti-inflammatory and pro-inflammatory mediators in monocyte-derived macrophages (Chapter 10). SF from donors without any joint pathology was used as control, and the effect of the different types of SF was tested on non-activated macrophages (M0) and on macrophages activated by IFNγ and TNFα (M1 activation) or IL4 (M2 activation). We found that IL10 and IL1ra were modulated by the treatment with OA SF in M0 and M2 conditions. The effect on IL10 was lost in M1 conditions probably due to the high up-regulation induced by the treatment with IFNγ and TNFα. Our results support the idea that arthritic SF is for macrophages a less pro-inflammatory environment compared to control SF. This may mimic the macrophage situation in the joint, where feedback mechanisms are induced to counteract the ongoing pro-inflammatory processes.
Altogether our findings highlight the complexity and multiplicity of factors that should be considered for the development of successful cell based treatments for early and late OA patients. We found that basic features of articular chondrocytes were affected by donors age and cartilage degeneration. We also found that expanded OA ACs did not exert a significant chondroinductive effect on co-cultured MSCs, suggesting that the evaluation of the clinical relevance of this approach in OA patients should strongly consider the impact of the de-differentiation state and pathological origin of ACs. Further investigations in this field are needed to verify whether it is possible to replicate the results obtained using non-expanded healthy ACs to co-cultures using expanded ACs from aged patients affected by osteoarthritis. These investigations may require the optimization of clinically approved protocols for expansion and re-differentiation of OA chondrocytes as well as the implementation of three-dimensional and dynamic culture systems. We demonstrated that low-cost rapid prototyping techniques are a useful tool to develop high-throughput systems for the culture of 3D cell aggregates and to generate patterned scaffolds that allow the controlled spatial disposition of different cell types. We also showed that the use of perfusion bioreactors for the dynamic culture of 3D constructs can improve the quality of the engineered tissue, granting a more homogeneous and efficient distribution of nutrients and cells throughout the construct. In order to overcome the limitations related to the use of ACs, MSCs can be considered as promising alternative cell candidates. Here, the identification of specific subsets of MSCs displaying a peculiar commitment should drive the selection of the most suitable cell source. Indeed, as we demonstrated for IFP-MSCs and ASCs, despite common features, specific populations of MSCs harvested from different anatomical sites have intrinsic features that make them more or less suitable for a specific application.
Cell-based therapies aiming at cartilage restoration cannot be currently applied to late stage OA patients. However, in this category of patients cell-based approaches can be developed to face issues that are critical in implant technology, such as poor osseointegration. As we proposed here, osteoprogenitor cells, osteoinductive factors, and macroporous metals can be combined to generate a bioactive implant with improved osseointegration ability. This approach could be used to generate “off-the-shelf” implants pre-loaded with osteoinductive factors that can be seeded with autologous BMSCs with a fully intra-operative approach.
Finally, when developing cell-based approaches for OA patients, the inflammatory state of the OA joint cannot be neglected. We found that macrophage transcriptional expression was affected by OA synovial fluid. This suggests that OA environments may also induce alterations in the re-implanted cells and highlights the need for better in vitro models to evaluate the response of cells and engineered tissues to a diseased environment.
In conclusion, to develop novel cell-based approaches for the treatment of OA basic and translational studies should take into account multiple factors that may affect the clinical outcome, such as the impaired phenotype of OA chondrocytes, the peculiar commitment of specific populations of MSCs, and the impact of inflammatory environment of OA joints
Potenziale osteogenico in vitro di cellule staminali mesenchimali isolate da tessuto adiposo di coniglio (rbASC, rabbit Adipose-derived Stem Cells) : risorsa futura per la rigenerazione di tessuto osseo in modelli preclinici
No full textNegli ultimi anni il nostro laboratorio si sta interessando alla caratterizzazione e al differenziamento di cellule staminali mesenchimali prelevate da tessuto adiposo umano (ASC, Adipose-derived Stem Cells), al fine di proporre nuovi approcci terapeutici che utilizzano cellule staminali mesenchimali (MSC) nell’ambito dell’ ingegneria tissutale (de Girolamo et al. TERM 2007, IJAO 2008).
In questo studio ci siamo occupati della caratterizzazione e del differenziamento verso la linea osteogenica di ASC prelevate dal tessuto adiposo di coniglio (rbASC) per la creazione di un modello animale di rigenerazione dei tessuti muscolo-scheletrici
Cellule rbASC, isolate da 7 conigli, sono risultate altamente proliferanti e presentano, nei primi passaggi in coltura, una capacità clonogenica intorno al 15%. La loro capacità differenziativa verso la linea osteogenica è stata dimostrata valutando l’incremento, rispetto alle cellule indifferenziate, dell’attività di fosfatasi alcalina, di deposizione di matrice extracellulare calcificata e l’induzione di osteonectina.
Inoltre cellule rbASC, differenziate e non, in presenza di scaffold (idrossiapatite e Orthoss®) sono in grado di produrre livelli di fosfatasi alcalina e di matrice calcificata superiori a quelli prodotti da cellule mantenute su polistirene.
Si può quindi affermare che il tessuto adiposo di coniglio, come precedentemente dimostrato per quello umano, contiene numerose cellule staminali mesenchimali multipotenti che si mantengono facilmente in coltura allo stato indifferenziato e che, in presenza di opportuni stimoli chimici e fisici, differenziano verso cellule della linea osteogenica.
Abbiamo quindi progettato uno studio in vivo in cui cellule rbASC autologhe verranno utilizzate in un modello pre-clinico di difetti ossei in associazione a opportuni supporti
Influence on chondrogenesis of human osteoarthritic chondrocytes in co-culture with donor-matched mesenchymal stem cells from infrapatellar fat pad and subcutaneous adipose tissue
No full textCo-culture of mesenchymal stem cells (MSCs) and articular chondrocytes (ACs) has been proposed for autologous cartilage cell-based therapies, to overcome the issues associated to limited availability of articular chondrocytes (ACs). To evaluate the potentiality of a co-culture approach in aged osteoarthritic patients, MSCs from infrapatellar fat pad (IFP-MSCs) and knee subcutaneous adipose tissue (ASCs) were co-cultured with donor-matched osteoarthritic, expanded and cryopreserved, ACs in a 75%/25% ratio. Co-cultures were prepared also from nasal chondrocytes (NCs) to evaluate their possible use as an alternative to ACs. Pellets were differentiated for 14 days, using mono-cultures of each cell type as reference. Chondrogenic genes SOX9, COL2A1, ACAN were less expressed in co-cultures compared to ACs and NCs. Total GAGs content in co-cultures did not differ significantly from values predicted as the sum of each cell type contribution corrected for the co-culture ratio, as confirmed by histology. No significant differences were observed for GAGs/DNA in mono-cultures, demonstrating a reduced chondrogenic potential of ACs and NCs. In conclusion, a small percentage of expanded and cryopreserved ACs and NCs did not lead to IFP-MSCs and ASCs chondro-induction. Our results suggest that chondrogenic potential and origin of chondrocytes may play a relevant role in the outcome of co-cultures, indicating a need for further investigations to demonstrate their clinical relevance in the treatment of aged osteoarthritic patients
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
Adipose-derived stem cells (ASCs) for the treatment of osteochondral defects : comparison between human and porcine ASCs for a future pre-clinical model
No full textAdipose-derived stem cells (ASCs) with their osteogenic and chondrogenic potential may represent a novel approach which may substitute or ameliorate the currently available therapies for the treatment of osteochondral defects due to trauma or osteo-degenerative diseases affecting joints.
We characterized pASCs (pig Adipose-derived Stem Cells) and evaluated their osteogenic and chondrogenic potential comparing them to hASCs (human Adipose-derived Stem Cells).
The number of hASCs per ml of raw adipose tissue (4.7x105±3.4x105, n=11) was higher compared to the number of pASCs (1.8x105±4.7x104, n=5). One week after isolation both cellular populations start to constantly proliferate obtaining about 107-108 hASCs and 108-109 pASCs in four weeks of culture. Both hASCs and pASCs show the typical fibroblast-like morphology of mesenchymal stem cells, maintained during their life span.
ASCs from both human and pig are highly clonogenic with a percentage of colony forming units of about 15% until the IV passage in culture.
The osteogenic differentiation of hASCs and pASCs in the absence or in the presence of clinical-grade hydroxyapatite granules (HA) was analyzed by ALP activity quantification. In the absence of scaffold, undifferentiated hASCs show about 10-fold higher ALP basal levels respect to pASCs, however both cellular populations possess a similar ability to respond to the differentiative osteogenic stimuli with an increased ALP activity of about 100% in hASCs and pASCs differentiated for 14 days.
The presence of HA granules induces a significant increase in ALP level both for undifferentiated and differentiated hASCs and pASCs, in comparison to cells grown on monolayer, confirming our previous data about the in vitro HA osteo-inductive properties. Interestingly, we observed a synergistic effect produced by the combination of scaffold and osteogenic medium, supporting the future clinical applications of HA in association with in vitro differentiated ASCs.
Moreover, both hASCs and pASCs, aggregated into micromasses where the physiological conditions of cartilage are partially recreated, have been differentiated towards cells of the chondrogenic lineage in the presence of 1% FBS and 10 ng/ml TGF-β1 for 21 days. Both cell types express an abundant amount of sulfated glycosaminoglycans (GAGs) showing a significant increase of about 115% and 95% in the GAGs content in comparison to undifferentiated cells.
These data demonstrate that hASCs and pASCs share common features and possess a similar osteogenic and chondrogenic differentiative ability, supporting the idea that the pre-clinical autologous ASCs reimplantation model in pig might be predictive of the behaviour of ASCs in a future clinical model of cell therapy
- …
